Novel Mechanism of the Pericyte-Myofibroblast Transition in Renal Interstitial Fibrosis: Core Fucosylation Regulation.
Novel Mechanism of the Pericyte-Myofibroblast Transition in Renal Interstitial Fibrosis: Core Fucosylation Regulation.
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肾间质纤维化中周细胞-肌成纤维细胞转变的新机制：核心岩藻糖基化调控
DOI：
10.1038/s41598-017-17193-5
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发表时间：
2017-12-05
影响因子：
4.6
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Wang N;Deng Y;Liu A;Shen N;Wang W;Du X;Tang Q;Li S;Odeh Z;Wu T;Lin H
周细胞已被确定为肾间质纤维化（RIF）中肌成纤维细胞的主要来源。在RIF过程中，几种信号传导途径（主要是TGF-β和PDGF途径）的过度活化启动了周细胞-肌成纤维细胞的转变。这两个途径中的关键受体已被证明是由岩藻糖基转移酶8（FUT 8），催化核心岩藻糖基化的酶修饰。本研究推测核心岩藻糖基化可能在调节RIF中的周细胞转变中起重要作用。数据显示，核心岩藻糖基化随着伊加肾病（IgAN）患者RIF程度的增加而增加。同样，在单侧输尿管闭塞（UUO）小鼠模型和周细胞转变的体外模型中，周细胞的核心岩藻糖基化均增加。腺病毒介导的FUT 8 shRNA在体内和FUT 8 siRNA在体外抑制核心岩藻糖基化显著减少周细胞转化和RIF。此外，TGF-β/Smad和PDGF/ERK途径的激活被核心岩藻糖基化抑制所阻断。总之，核心岩藻糖基化可能通过修饰TGF-β/Smad和PDGF/ERK途径来调节RIF中的周细胞转变。糖基化可能是预防RIF的一个新的“中枢”靶点。
Pericytes have been identified as a major source of myofibroblasts in renal interstitial fibrosis (RIF). The overactivation of several signaling pathways, mainly the TGF-β and PDGF pathways, initiates the pericyte-myofibroblast transition during RIF. Key receptors in these two pathways have been shown to be modified by fucosyltransferase 8 (FUT8), the enzyme that catalyzes core fucosylation. This study postulated that core fucosylation might play an important role in regulating the pericyte transition in RIF. The data showed that core fucosylation increased with the extent of RIF in patients with IgA nephropathy (IgAN). Similarly, core fucosylation of pericytes increased in both a unilateral ureteral occlusion (UUO) mouse model and anin vitromodel of pericyte transition. Inhibition of core fucosylation by adenoviral-mediatedFUT8shRNAin vivoandFUT8siRNAin vitrosignificantly reduced pericyte transition and RIF. In addition, the activation of both the TGF-β/Smad and PDGF/ERK pathways was blocked by core fucosylation inhibition. In conclusion, core fucosylation may regulate the pericyte transition in RIF by modifying both the TGF-β/Smad and PDGF/ERK pathways. Glycosylation might be a novel “hub” target to prevent RIF.
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DOI：
10.1146/annurev-pathol-020712-163930
发表时间：
2013-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Duffield JS;Lupher M;Thannickal VJ;Wynn TA
通讯作者：
Wynn TA
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
19.6
作者：
Bijkerk, Roel;de Bruin, Ruben G.;van Zonneveld, Anton Jan
通讯作者：
van Zonneveld, Anton Jan
影响因子：
6
作者：
Lin, Shuei-Liong;Kisseleva, Tatiana;Duffield, Jeremy S.
通讯作者：
Duffield, Jeremy S.
影响因子：
4.3
作者：
Ihara, H;Ikeda, Y;Taniguchi, N
通讯作者：
Taniguchi, N